The present invention relates generally to the use of bioactive molecules to ocular tissues and, more specifically, to the delivery of lutein to the macula using iontophoresis.
Lutein (and zeaxanthin) are associated with reducing the risk of developing AMD (Age-related Macular Degeneration) and cataract extraction due to its antioxidant and photoprotective effects, and its exclusive distribution in the eye macula1. Age is one of the most important risk factors for AMD, typically affecting individuals over 50 years old2-4. There are two types of AMD, ‘dry AMD’ and ‘wet AMD’. Dry AMD develops when macular cells become damaged as a result of waste product accumulation called “drusen”. It is the most common and least serious type of AMD. An estimated high number of those that present dry AMD symptoms will develop wet AMD, which develops when abnormal blood vessels from underneath the macula grow and lead to irreversible cell damage2-4.
Lutein has been widely used through oral supplementation with the rationale that systemic circulation can bring lutein to the coroidal circulation for uptake into the macula, through xanthophyll-binding protein5. However, several reports demonstrate that only a small percentage of lutein reaches the macula6-8. Moreover, due to eye barrier limits, therapeutic treatments in the posterior eye segment are difficult. Since the eye is protected by the tear film, corneal, vitreous, blood-retinal and blood-aqueous barriers, it is very difficult to deliver drugs to the eye, particularly to the retina, in sufficient concentrations and with minimal side-effects9, 10. In-situ applications have been used to overcome this problem; however, slow delivery systems, such as implants, are very invasive and expensive. Over the past few years, the results of many studies have highlighted the risks of these treatments11, 12.
Recently, intra-vitreous injections of lutein have been used to stain specific preretinal membranes and other eye structures during surgery13-16. This has been the first data on in-situ delivery of lutein towards the macula, exploiting lutein's intrinsic staining effect. Lutein's potential of delaying AMD progression and putative neuroprotective action shown in different trials has not yet been proven through in-situ application following intraocular delivery. Intravitreous injection of lutein for a prevention purpose may be too invasive as a strategy of delivering lutein to the macula, with the disadvantage of poor patient acceptance.
Ocular iontophoresis is a minimally invasive method used to propel by electrical force high concentrations of target molecules transsclerally or/and transcorneally. It uses a small electrical current applied to an iontophoretic chamber containing the molecule of interest and vehicle17. Several reports revealed that lutein, which is found in high concentrations in the macula of the human eye, has the potential of delaying AMD progression, in addition to potential neuroprotective action18-20.
Here we report a novel way of delivering lutein to the retina, so its presence in the parafovea macular region can be enhanced significantly and thereby delay the progression of AMD and protect retinal endothelial cells. Different iontophoresis delivery systems for ophthalmic use have been created and have been used to safely and effectively deliver medication to both the anterior and posterior segments of the human eye21. With this technology, it is possible to deliver significant amounts of bioactive molecules, including macromolecules, across the cornea and sclera. In the work reported here, a lutein emulsion has been diffusively delivered to the macula by iontophoresis22-23. The idea was to develop a minimally invasive method of propelling high concentrations of charged lutein, transclerally or/and transcorneally by iontophoresis. We have assessed the distribution and concentration of lutein in the different ocular tissues using two-photon microscopy, Raman spectroscopy and HPLC after scleral and corneal iontophoretic application. The main advantage of this approach is to use of a medical device that is safer and easier to have patient compliance, avoiding the complications of frequent and high dose injections or surgical implantations. This procedure can be performed quickly in the doctor's office during a normal eye care appointment with no need of a surgical environment.